We propose to establish the Moffitt Imaging Biomarker Validation Center (MIBVAC) focused on imaging biomarker validations for early cancer detection and accurate risk assessments by leveraging our team of strong experts, resources, planned imaging biomarker validation studies, and analysis and network collaboration structures. In previous studies we have demonstrated that various measurements from breast images quantify breast cancer risk. The large cooperative National Lung Screening Trial (NLST) also showed a significant survival improvement for individuals screened by low dose CT compared to those screened with conventional radiography. Additionally, we have recently shown that CT image analysis (radiomics) can improve classification in this data set. However, due to difficulties in obtaining accurate and reproducible measurements and high false-positive rates of current imaging, cancer imaging biomarkers have not been routinely incorporated into clinical risk assessment. If these imaging biomarkers can be accurately tailored at the individual level, their impact will be significantly improved for early cancer detection and intervention. MIBVAC plans to achieve this challenging yet quite achievable goal by rigorously evaluating and validating these imaging biomarkers for rapid translation into clinical and practical applications. We have four specific aims: (Aim 1) Establish breast imaging resources for EDRN both with our existing and new case-control datasets of breast images and to evaluate and validate breast imaging biomarkers based on newly-established case-control dataset of digital breast tomosynthesis (TS) images, (Aim 2) Evaluate and validate lung imaging biomarkers for early detection of cancer first based on NLST low-dose CT (LDCT) cohorts and then expanding with a newly-established case-control cohort of higher resolution LDCT, (Aim 3) Conduct validation studies with imaging biomarkers for EDRN partners and others for other malignancies, and (Aim 4) Refine and validate imaging biomarkers analytically for early detection of breast, lung, and other cancers and to construct MIBVAC imaging data and specimen resources for EDRN collaborations and sharing.